A comprehensive review of natural product-derived compounds acting on P2X7R: The promising therapeutic drugs in disorders.

BACKGROUND: The P2X7 receptor (P2X7R) is known to play a significant role in regulating various pathological processes associated with immune regulation, neuroprotection, and inflammatory responses. It has emerged as a potential target for the treatment of diseases. In addition to chemically synthesized small molecule compounds, natural products have gained attention as an important source for discovering compounds that act on the P2X7R. PURPOSE: To explore the research progress made in the field of natural product-derived compounds that act on the P2X7R. METHODS: The methods employed in this review involved conducting a thorough search of databases, include PubMed, Web of Science and WIKTROP, to identify studies on natural product-derived compounds that interact with P2X7R. The selected studies were then analyzed to categorize the compounds based on their action on the receptor and to evaluate their therapeutic applications, chemical properties, and pharmacological actions. RESULTS: The natural product-derived compounds acting on P2X7R can be classified into three categories: P2X7R antagonists, compounds inhibiting P2X7R expression, and compounds regulating the signaling pathway associated with P2X7R. Moreover, highlight the therapeutic applications, chemical properties and pharmacological actions of these compounds, and indicate areas that require further in-depth study. Finally, discuss the challenges of the natural products-derived compounds exploration, although utilizing compounds from natural products for new drug research offers unique advantages, problems related to solubility, content, and extraction processes still exist. CONCLUSION: The detailed information in this review will facilitate further development of P2X7R antagonists and potential therapeutic strategies for P2X7R-associated disorders.

Huoxue Qianyang Qutan Recipe Protects against Early Renal Damage Induced by Obesity-Related Hypertension via the SIRT1/NF-κB/IL-6 Pathway: Integrating Network Pharmacology and Experimental Validation-Based Strategy.

Obesity is recognized as not only a major contributing factor to cardiovascular diseases but also an independent risk factor for end-stage renal disease. Previous studies have found that Huoxue Qianyang Qutan Recipe (HQQR) could reduce urinary microalbumin in patients with obesity-related hypertension (OBH). However, the renal protective activity of HQQR in OBH and its molecular targets involved remains ambiguous. In this work, we investigate the mechanism of HQQR against OBH-induced early renal damage using integrating network pharmacology and experimental validation-based strategy. First, via network pharmacology, IL-6 is identified as one of the key targets of HQQR against early renal damage in hypertension, and inhibition of inflammation is a crucial process. Second, in in vivo experiments, HQQR can lower blood pressure, lose weight, and restore metabolic abnormalities in OBH rats, which could be associated with the effects on protecting early renal damage. Finally, in the mechanism, HQQR increases SIRT1 mRNA and protein expression consistent with reduction of NF-κB acetylation and suppressed the p65-mediated inflammatory signaling pathway. As a result, HQQR robustly inhibits OBH-induced renal inflammation by reducing IL-6 mRNA and protein levels in the renal tissue and the release of IL-6 in serum of OBH rats. This study aims to provide a multimethod (network pharmacology-animal experiment) and multilevel (component-target-pathway) strategy for the prevention and treatment of OBH-induced target organ damage by traditional Chinese medicine.

The efficacy of ginseng-containing traditional Chinese medicine in patients with acute decompensated heart failure: A systematic review and meta-analysis.

Objective: To evaluate the efficacy of ginseng-containing traditional Chinese medicine (TCM) for acute decompensated heart failure (ADHF). Methods: Seven databases were included from establishment until 10 July 2022. Pooled data were analyzed with random-effects model. The risk of bias was measured by the risk of bias tool for randomized trials (RoB 2). Modified Jadad scale score was used to assess the quality of including studies. The meta-analysis was performed with RevMan 5.3. Trial sequential analysis was assessed to avoid type I errors. We have registered our protocol in PROSPERO (CRD42021267742). Results: Twenty-eight articles were included. The results demonstrated that compared with conventional western therapy (WT), ginseng-containing TCM combined with WT further improved clinical efficacy (RR: 1.25, 95% CI: 1.20-1.29, p < 0.00001, I2 = 8%), left ventricular ejection fraction (LVEF) (MD: 5.80, 95% CI: 4.86-6.74, p < 0.00001, I2 = 89%), stroke volume (MD: 13.80, 95% CI: 12.66-14.95, p < 0.00001, I2 = 93%), 6-min walk test (MD: 53.03, 95% CI: 20.76-85.29, p = 0.001, I2 = 97%), decreased 6-month rehospitalization (RR: 0.44, 95% CI: 0.18-1.11, p = 0.08, I2 = 0%), brain natriuretic peptide (MD: 188.12, 95% CI: 248.13 to -128.11, p < 0.00001, I2 = 94%), N-terminal pro-B-type natriuretic peptide (MD = -503.29; 95% CI: 753.18 to -253.40, p < 0.0001, I2 = 89%) and Minnesota living heart failure questionnaire scores (MD: 9.68, 95% CI: 13.67 to -5.70, p < 0.00001, I2 = 83%). The ROB2 assessment and modified Jaded scores showed most studies included were with some concerns. Conclusion: Compared with WT alone, ginseng-containing TCM is a possible way to benefit ADHF patients. However, limited by the quality of including trials, more high-quality studies are needed to provide reliable evidence.

Analysis of Anesthesia Effect of Dexmedetomidine in Clinical Operation of Replantation of Severed Finger.

Brachial plexus block commonly used in finger replantation has the advantages of simple operation, small side effects, and stable circulation, but it has inherent problems such as imperfect block range, slow onset of anesthesia, and short maintenance time of anesthesia. In order to explore the reliable clinical anesthesia effect, this paper uses experimental investigation methods to study the effect of dexmedetomidine in clinical surgery of replantation of severed fingers. Moreover, this paper uses comparative test methods, uses statistical methods to process test data, and uses intuitive methods to display test results. Finally, this paper verifies the reliability of dexmedetomidine in replantation of severed finger through comparative analysis and verifies that the anesthesia method proposed in this paper has certain user satisfaction through parameter survey.

High humidity aggravates the severity of arthritis in collagen-induced arthritis mice by upregulating xylitol and L-pyroglutamic acid.

BACKGROUND: Humidity was an unfavorable factor for patients with rheumatoid arthritis (RA). RA disease activity was severe in high humidity conditions. However, there is no evidence to demonstrate the effects of humidity on arthritis in the animal experiments and explore its relevant mechanism. METHODS: Using the DBA/1 mice, this study addressed the effects of a high humidity (80 ± 5%) on arthritis in collagen-induced arthritis (CIA) mice. Then, this study used the gas chromatography-mass spectrometer (GC-MS) to explore alterations in serum metabolome caused by the high humidity. Furthermore, xylitol and L-pyroglutamic acid, which were both significantly upregulated by the high humidity, were selected to further study their effects on arthritis in the CIA mice. RESULTS: The high humidity (80 ± 5%) could aggravate arthritis variables including increasing arthritis score and swelling, serum autoantibodies (anti-COII and anti-CCP), and proinflammatory cytokines (IL-6, IL-17A, and G-CSF). In addition, the high humidity could cause significant alterations in serum metabolome in the CIA mice. Xylitol and L-pyroglutamic acid were the representative serum metabolites that were significantly upregulated by the high humidity. Further experiments demonstrated that the supplementation of 0.4 mg/mL xylitol in drinking water after inducing the CIA model and 2.0 mg/mL in drinking water before inducing the CIA model could both aggravate arthritis in the CIA mice. CONCLUSIONS: These data demonstrated that high humidity was not beneficial for arthritis development and its mechanism might be associated with xylitol and L-pyroglutamic acid.

Theoretical Study of the Molecular Mechanism of Maxingyigan Decoction Against COVID-19: Network Pharmacology-based Strategy.

AIM AND OBJECTIVE: Maxingyigan (MXYG) decoction is a traditional Chinese medicine (TCM) prescription. However, how MXYG acts against coronavirus disease 2019 (COVID-19) is not known. We investigated the active ingredients and the therapeutic targets of MXYG decoction against COVID-19. METHODS: A network pharmacology strategy involving drug-likeness evaluation, prediction of oral bioavailability, network analyses, and virtual molecular docking was used to predict the mechanism of action of MXYG against COVID-19. RESULTS: Thirty-three core COVID-19-related targets were identified from 1023 gene targets through analyses of protein-protein interactions. Eighty-six active ingredients of MXYG decoction hit by 19 therapeutic targets were screened out by analyses of a compound-compound target network. Via network topology, three "hub" gene targets (interleukin (IL-6), caspase-3, IL-4) and three key components (quercetin, formononetin, luteolin) were recognized and verified by molecular docking. Compared with control compounds (ribavirin, arbidol), the docking score of quercetin to the IL-6 receptor was highest, with a score of 5. Furthermore, the scores of three key components to SARS-CoV-2 are large as 4, 5, and 5, respectively, which are even better than those of ribavirin at 3. Bioinformatics analyses revealed that MXYG could prevent and treat COVID-19 through anti-inflammatory and immunity-based actions involving activation of T cells, lymphocytes, and leukocytes, as well as cytokine-cytokine-receptor interaction, and chemokine signaling pathways. CONCLUSION: The hub genes of COVID-19 helped to reveal the underlying pathogenesis and therapeutic targets of COVID-19. This study represents the first report on the molecular mechanism of MXYG decoction against COVID-19.

Simiao Decoction Alleviates Gouty Arthritis by Modulating Proinflammatory Cytokines and the Gut Ecosystem.

Simiao decoction, a classical traditional Chinese medicine (TCM) formula, has been widely used for thousands of years due to its safety and efficiency in treating gouty arthritis. Utilizing serum proinflammatory cytokines and gut ecosystems, this study elucidated the mechanisms of alleviating gouty arthritis by Simiao decoction. Simiao decoction (4.0, 8.0, and 16.0 g/kg) was orally administered to gouty arthritis mice and febuxostat was given as a positive control. The spleen, kidney, and liver indexes indicated that Simiao decoction was safe for the treatment of gouty arthritis in C57BL/6 mice. Besides, our study demonstrated that Simiao decoction was effective for reducing the level of serum uric acid and decreasing MPO, XOD, and ADA activity, as well as alleviating gouty-related symptoms, such as foot swelling and pain. Moreover, Simiao decoction could also reduce some specific serum proinflammatory cytokines including IL-1ß, IL-9, IFN-γ, MIP-1α and MIP-1ß. We then surveyed the effects of Simiao decoction on the gut ecosystems in a systematic manner by combining network pharmacology, ELISA, western blot, and illumina sequencing. In the murine of model of gouty arthritis, Simiao decoction could suppress NLRP3 inflammasomes expression, reduce gut apoptosis through modulating TNF-α, Caspase 8, and AIFM1 protein expressions, affect lipid metabolism by regulating APOB, LPL, PPARα protein expressions and restore gut microbiota via reducing potential pathogens. Overall, these findings suggested that Simiao decoction was an effective therapeutic drug for gouty arthritis and the gut ecosystem might act as a potential anti-inflammatory target of Simiao decoction.

Chemical and antihyperglycemic activity changes of ginseng pectin induced by heat processing.

Six pectic polysaccharides were obtained from white ginseng (GPW-1 and GPW-2), red ginseng (GPR-1 and GPR-2, steamed ginseng at 100°C) and steamed ginseng (GPS-1 and GPS-2, steamed ginseng at 120°C) by combination of water extraction, ion-exchange and gel permeation chromatographies. Based on the data from monosaccharide composition and (13)C NMR analysis, GPW-1, GPR-1 and GPS-1 were identified as type-I rhamnogalacturonan (RG-I)-rich pectins, GPW-2, GPR-2 and GPS-2 were homogalacturonan (HG)-rich pectins with different degrees of methyl-esterification. Remarkably, GalA increased with the increase of processing temperatures in these six fractions, which might be caused by the transformation of esterified GalA into un-esterified form during heat processing. In vivo animal experiments showed that GPs exhibited significant antiohyperglycemic and antioxidant activities in alloxan-induced diabetic mice, and the effects increased with the processing temperature, with the most potent activity in GPS.

Antioxidant activities of the oligosaccharides from the roots, flowers and leaves of Panax ginseng C.A. Meyer.

The chemical characterization and antioxidant activities of water-soluble ginseng oligosaccharides from roots (WGOS-R), flowers (WGOS-F) and leaves (WGOS-L) of Panax ginseng C.A. Meyer obtained by hot water extraction were investigated. The sugar content of WGOS-R, WGOS-F and WGOS-L were 95.87%, 87.07% and 83.09%, respectively. The ginsenosides and total phenols content decreased in the order of WGOS-L>WGOS-F>WGOS-R. WGOS-R comprised only Glc, WGOS-F and WGOS-L comprised Glucose (Glc) and Rhamnose (Rha) in a molar ratio of 6.0:1.0 and 7.0:1.0, respectively. In vitro antioxidant tests showed that WGOS-R exhibited higher antioxidant activity than WGOS-F and WGOS-L. In vivo antioxidant tests showed that WGOS-R significantly enhanced activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capability (T-AOC) in the serum and liver and decreased malondialdehyde (MDA) level in the serum and liver.

Anti-tumour and immunomodulatory activities of oligosaccharides isolated from Panax ginseng C.A. Meyer.

Water-soluble ginseng oligosaccharides (WGOS) composed of D-glucose with a degree of polymerisation ranging from 2 to 14 were obtained from Panax ginseng C.A. Meyer. In this study, the anti-tumour and immunoregulatory effects of WGOS were evaluated in Hepatoma-22 (H22)-bearing mice. Treatment with WGOS inhibited tumour growth in vivo and significantly increased relative spleen and thymus weight, serum tumour necrosis factor-α level, spleen lymphocyte proliferation, natural killer cell activity, phagocytic function and nitric oxide production secreted by macrophage in H22-bearing mice. However, no direct cytotoxicity was detected. Therefore, the anti-tumour activity of WGOS may be related to their immunomodulatory effects.

Photobleaching response of different sources of chromophoric dissolved organic matter exposed to natural solar radiation using absorption and excitation-emission matrix spectra.

CDOM biogeochemical cycle is driven by several physical and biological processes such as river input, biogeneration and photobleaching that act as primary sinks and sources of CDOM. Watershed-derived allochthonous (WDA) and phytoplankton-derived autochthonous (PDA) CDOM were exposed to 9 days of natural solar radiation to assess the photobleaching response of different CDOM sources, using absorption and fluorescence (excitation-emission matrix) spectroscopy. Our results showed a marked decrease in total dissolved nitrogen (TDN) concentration under natural sunlight exposure for both WDA and PDA CDOM, indicating photoproduction of ammonium from TDN. In contrast, photobleaching caused a marked increase in total dissolved phosphorus (TDP) concentration for both WDA and PDA CDOM. Thus TDN:TDP ratios decreased significantly both for WDA and PDA CDOM, which partially explained the seasonal dynamic of TDN:TDP ratio in Lake Taihu. Photobleaching rate of CDOM absorption a(254), was 0.032 m/MJ for WDA CDOM and 0.051 m/MJ for PDA CDOM from days 0-9, indicating that phototransformations were initially more rapid for the newly produced CDOM from phytoplankton than for the river CDOM. Extrapolation of these values to the field indicated that 3.9%-5.1% CDOM at the water surface was photobleached and mineralized every day in summer in Lake Taihu. Photobleaching caused the increase of spectral slope, spectral slope ratio and molecular size, indicating the CDOM mean molecular weight decrease which was favorable to further microbial degradation of mineralization. Three fluorescent components were validated in parallel factor analysis models calculated separately for WDA and PDA CDOM. Our study suggests that the humic-like fluorescence materials could be rapidly and easily photobleached for WDA and PDA CDOM, but the protein-like fluorescence materials was not photobleached and even increased from the transformation of the humic-like fluorescence substance to the protein-like fluorescence substance. Photobleaching was an important driver of CDOM and nutrients biogeochemistry in lake water.

Interaction between amylose and tea polyphenols modulates the postprandial glycemic response to high-amylose maize starch.

High-amylose maize starch (HAM) is a common source material to make resistant starch with its high content of amylose (>70%). In the current investigation, the self-assembly of amylose in the presence of bioactive tea polyphenols (TPLs) and resulting slow digestion property of starch were explored. The experimental results using a mouse model showed a slow digestion property can be achieved with an extended and moderate glycemic response to HAM starch cocooked with TPLs. Further studies using a dilute aqueous amylose solution (0.1%, w/v) revealed an increased hydrodynamic radius of amylose molecules, indicating that TPLs could bridge them together, leading to increased molecular sizes. On the other hand, the bound TPLs interrupted the normal process of amylose recrystallizaiton evidenced by a decreased viscosity and storage modulus (G') of HAM (5%) gel, a rough surface of the cross-section of HAM film, and decreased short-range orders examined by Fourier transform infrared spectral analysis. Single-step degradation curves in the thermal gravimetric profile demonstrated the existence of a self-assembled amylose-TPL complex, which is mainly formed through hydrogen bonding interaction according to the results of iodine binding and X-ray powder diffraction analysis. Collectively, the amylose-TPL complexation influences the normal self-assembling process of amylose, leading to a low-ordered crystalline structure, which is the basis for TPLs' function in modulating the digestion property of HAM starch to produce a slowly digestible starch material that is beneficial to postprandial glycemic control and related health effects.

Effect of green tea catechins on the postprandial glycemic response to starches differing in amylose content.

The effect of tea polyphenols (TPLs), specifically tea catechins, on the postprandial glycemic response to cooked starches differing in amylose contents was investigated. The in vivo test using a mouse model showed a moderate reduction of the postprandial glycemic response to co-cooked normal (containing 27.8% amylose) or waxy corn starch with 10% TPLs (dry weight of starch), while an augmented glycemic response with a delayed blood glucose peak was observed when high amylose corn starch (HAC, containing 79.4% amylose) was used as the starch component. Enzyme kinetics results demonstrated that TPLs noncompetitively inhibit the digestion of waxy or normal corn starch, while the digestion rate of HAC starch was increased in the presence of TPLs, which supports the observed postprandial glycemic responses. Further studies using X-ray powder diffraction showed that the diffraction intensity (area under the diffraction curves) of normal and HAC starch was increased by 45% and 74%, respectively, whereas no change was observed for waxy corn starch. Consistently, dynamic laser light scattering studies using a solution of pure amylose showed an increased hydrodynamic radius of amylose molecules from ∼54 nm to ∼112 nm in the presence of TPLs. These experimental results indicate that there might exist an interaction between TPLs and amylose, which facilitates the association of amylose molecules to form a special nonordered structure that can produce a high and sustained postprandial glycemic response. Thus, a combination of tea polyphenols and specific starches could be used to manipulate postprandial glycemic response for glycemic control and optimal health.

[Etiology and treatment of bladder spasm associated with benign prostatic hyperplasia].

OBJECTIVE: To investigate the etiology and treatment of bladder spasm associated with benign prostatic hyperplasia (BPH). METHODS: Urodynamic tests were performed in 102 cases of BPH before operation. The correlation of bladder spasm with aging, international prostate symptom score (IPSS), quality of life, prostatic volume, operation methods and urodynamic indexes was studied by t and chi2 tests. RESULTS: The incidences of bladder spasm in the lower compliant bladder and unstable bladder were 32.1% (9/28) and 42.5% (13/20), and those after suprapubic prostatectomy and transurethral resection of the prostate (TURP) were 50.9% (26/51) and 23.3% (12/51). There was significant difference between operation methods (P < 0.05). CONCLUSION: Bladder spasm easily develops in the lower compliant bladder and unstable bladder, especially after suprapubic prostatectomy. TURP might decrease the incidence of bladder spasm after BPH operation.